EBV-Related Lymphoproliferative Diseases: A Review in Light of New Classifications

Abstract

Epstein-Barr virus (EBV) is a prevalent virus that can be detected in the vast majority of the population. Most people are asymptomatic and remain chronically infected throughout their lifetimes. However, in some populations, EBV has been linked to a variety of B-cell lymphoproliferative disorders (LPDs), such as Burkitt lymphoma, classic Hodgkin lymphoma, and other LPDs. T-cell LPDs have been linked to EBV in part of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other uncommon histotypes. This article summarizes the current evidence for EBV-associated LPDs in light of the upcoming World Health Organization classification and the 2022 ICC classification.

Keywords: EBV; Lymphoproliferative diseases.

Figure 1

EBV-latency immunogenicity in different EBV-related lymphoproliferative diseases.

Figure 2

Extranodal NK/T cell lymphoma, nasal-type showing a diffuse infiltrate of lymphoid cell of various sizes with angiotropism, destruction of vessels, and necrosis (A, H/E, 100x). The neoplastic cells are diffusely and strongly positive for EBER (B, EBER cISH, 100x).

Figure 3

H&E staining (A, 200x) of multiple fragments from a submandibular lymph-node extensively replaced by a blastoid lymphoid population consisting of medium to large sized elements with thick irregular nuclei and prominent nucleoli, showing immunoreactivity for CD20 (B, 200x), CD5 (C, 200x), BCL-2 (D, 200x), cyclin D1 (E, 200x), SOX-11 (F, 200X) and concrete expression of EBER (G, 200x). Mitotic activity of this post-transplant blastoid mantle cell lymphoma is dispersed with a proliferative index (ki67) of 35–40% (H, 200x).

Figure 4

Lymphomatoid granulomatosis shows a polymorphous infiltrate of T-lymphocytes, macrophages, and plasma cells that displays an angiocentric and angiodestructive pattern, admixed with EBER+ Reed-Sternberg-like B-lymphoid cells (A: H/E, 100x; B: EBER cISH, 100x).

Figure 5

EBV-positive Hodgkin lymphoma comprises a polymorphous infiltrate of T- and B-cells, eosinophils, macrophages, and fibroblasts surrounding HRS cells (A: H/E, 100x). Neoplastic cells are strongly EBV-positive (B: EBER cISH, 100x).